Hepatitis C virus dynamics and cellular gene expression in uPA-SCID chimeric mice with humanized livers during intravenous silibinin monotherapy.

Legalon SIL (SIL) is a chemically hydrophilized version of silibinin, an extract of milk thistle (Silybum marianum) seeds that has exhibited hepatoprotective and antiviral effectiveness against hepatitis C virus (HCV) in patients leading to viral clearance in combination with ribavirin. To elucidate the incompletely understood mode of action of SIL against HCV, mathematical modelling of HCV kinetics and human hepatocyte gene expression studies were performed in uPA-SCID-chimeric mice with humanized livers. Chronically HCV-infected mice (n = 15) were treated for 14 days with daily intravenous SIL at 469, 265 or 61.5 mg/kg. Serum HCV and human albumin (hAlb) were measured frequently, and liver HCV RNA was analysed at days 3 and 14. Microarray analysis of human hepatocyte gene expression was performed at days 0, 3 and 14 of treatment. While hAlb remained constant, a biphasic viral decline in serum was observed consisting of a rapid 1st phase followed by a second slower phase (or plateau with the two lower SIL dosings). SIL effectiveness in blocking viral production was similar among dosing groups (median ε = 77%). However, the rate of HCV-infected hepatocyte decline, δ, was dose-dependent. Intracellular HCV RNA levels correlated (r = 0.66, P = 0.01) with serum HCV RNA. Pathway analysis revealed increased anti-inflammatory and antiproliferative gene expression in human hepatocytes in SIL-treated mice. The results suggest that SIL could lead to a continuous second-phase viral decline, that is potentially viral clearance, in the absence of adaptive immune response along with increased anti-inflammatory and antiproliferative gene expression in human hepatocytes.

A comparison of monomicrobial versus polymicrobial Enterococcus faecalis bacteriuria in a French University Hospital.

Enterococci are of considerable relevance in the hospital setting. Their most common location is the urinary tract, where they may be responsible for both colonization and infections. They are often associated with the presence of other microorganisms. The aim was to compare monomicrobial and polymicrobial Enterococcus faecalis bacteriuria. A retrospective study was performed on the demographic, clinical, and laboratory data of 299 patients who had presented with E. faecalis bacteriuria in 2012 at a University Hospital. The bacteriuria was polymicrobial in 46.1 % of cases and in 36.4 % of cases was responsible for a urinary tract infection. Infections appeared to be more prevalent in the polymicrobial than the monomicrobial group (42 % vs 32 %, p = 0.06). Half of the patients who presented with urinary tract colonization received antibiotic treatment (54/ out of 10). A multivariate analysis adjusted for age (adjusted odds ratio [AOR] = 1.02 per year, p = 0.006), gender (AOR = 2.2, p = 0.007), and clinical classification (colonization or infection, AOR = 1.6, p = 0.091), showed that diabetes mellitus (AOR = 2.0, p = 0.04), hospital length of stay exceeding 28 days (AOR = 2.0, p = 0.03), and presence of a urinary catheter (AOR = 2.4, p = 0.001) were all factors associated with polymicrobial E. faecalis bacteriuria. A reduction in the length of hospital stay and the use of urinary catheters would appear to be required to decrease the incidence of urinary tract colonization and infections by polymicrobial E. faecalis. Improper use of antibiotics to treat urinary tract colonization remains a major concern.

[Tegumentary leishmaniasis in area with epidemic levels of transmission, Salta, Argentina, 1998]. / Leishmaniosis tegumentaria en un área con niveles epidémicos de transmisión, Salta, Argentina, 1998.

The incidence of tegumentary leishmaniasis increased in October 1997, in an area close to Oran city, province of Salta. The leishmaniasis' epidemiology and the entomology of this outbreak were studied during June 1998 at Paraje Las Carmelitas and Río Blanco, places with high reported incidence. The prevalence of infection (Montenegro Skin Test reactive) was 171/1000 inhabitants in Paraje Las Carmelitas and 790/1000 in Río Blanco, while the rates of leishmaniasis' incidence (active ulcers) were 72/1000 and 790/1000. The prevalence differences among sex and age groups were not significant. The clinical and epidemiologic patterns were consistent with those reported in the area for Leishmania (Viannia) braziliensis. Lutzomyia intermedia was the prevalent species (96%) among 2577 Phlebotominae collected, Lu. shannoni, Lu. cortelezzii y Lu. migonei were also present. The results about distribution of prevalence by age, and spatial distribution of Phlebotominae supported deforestation-residual primary forest transmission hypotheses. Therefore, in Salta the epidemic outbreaks generated by extensive deforestation could be sustained and amplified because the human settlements are located close to the remaining primary forest "spots". Furthermore, in this scenario the risk of human-vector contact increases by the subsistence or recreational activities performed in secondary transitional forests, and the presence of domestic animals around the houses. The results are discussed in the frame of possible control strategies.

Leishmaniosis tegumentaria en un área con niveles epidémicos de transmisión, Salta, Argentina, 1998. / [Tegumentary leishmaniasis in area with epidemic levels of transmission, Salta, Argentina, 1998]

The incidence of tegumentary leishmaniasis increased in October 1997, in an area close to Oran city, province of Salta. The leishmaniasis epidemiology and the entomology of this outbreak were studied during June 1998 at Paraje Las Carmelitas and Río Blanco, places with high reported incidence. The prevalence of infection (Montenegro Skin Test reactive) was 171/1000 inhabitants in Paraje Las Carmelitas and 790/1000 in Río Blanco, while the rates of leishmaniasis incidence (active ulcers) were 72/1000 and 790/1000. The prevalence differences among sex and age groups were not significant. The clinical and epidemiologic patterns were consistent with those reported in the area for Leishmania (Viannia) braziliensis. Lutzomyia intermedia was the prevalent species (96

) among 2577 Phlebotominae collected, Lu. shannoni, Lu. cortelezzii y Lu. migonei were also present. The results about distribution of prevalence by age, and spatial distribution of Phlebotominae supported deforestation-residual primary forest transmission hypotheses. Therefore, in Salta the epidemic outbreaks generated by extensive deforestation could be sustained and amplified because the human settlements are located close to the remaining primary forest [quot ]spots[quot ]. Furthermore, in this scenario the risk of human-vector contact increases by the subsistence or recreational activities performed in secondary transitional forests, and the presence of domestic animals around the houses. The results are discussed in the frame of possible control strategies.

Clinical healing of antimony-resistant cutaneous or mucocutaneous leishmaniasis following the combined administration of interferon-gamma and pentavalent antimonial compounds.

In an open trial, longer courses of pentavalent antimonials (Sbv) at sub-optimal doses (10 mg/kg body weight), in association with recombinant human interferon-gamma (IFN-gamma) (100 micrograms/m2 of body surface area) were administered, by daily intramuscular injections, to 13 patients with diagnoses of cutaneous or mucocutaneous leishmaniasis unresponsive to Sbv. Four patients presented with large skin ulcers, and 9 had mucosal involvement as the main manifestation, the latter affecting the nose (3 cases), nose and septum (2 cases), nose and oral cavity (1 case), and nose, pharynx and larynx (3 cases). Except for one case with severe involvement of the upper respiratory tract, the lesions were fully resolved by the end of therapy (mean duration 40 +/- 12 [SD] d, range 30-60 d) in the 11 patients who completed therapy. The main side effects were headache and fever (7 cases), together with leucopenia and eosinophilia (4 cases). It is concluded that combined administration of low doses of Sbv plus IFN-gamma may provide a novel therapeutic approach for the treatment of antimony-resistant cutaneous or mucocutaneous leishmaniasis. The possible mechanisms by which IFN-gamma contributes to resolution of the disease are discussed.